The present invention relates to antimicrobial compositions and methods for use of those compositions in various medical applications. One of the major challenges of modern medical treatment is the prevention of infection by microbial organisms.
One area where this challenge is constantly presented is in infusion therapy. Infusion therapy is one of the most common health care procedures. Hospitalized, home care, and other patients receive fluids, pharmaceuticals, and blood products via vascular access devices inserted into the vascular system. Infusion therapy may be used to treat an infection, provide anesthesia or analgesia, provide nutritional support, treat cancerous growths, and maintain blood pressure and heart rhythm, among many other clinically significant uses.
Infusion therapy is facilitated by a vascular access device. The vascular access device may access a patient's peripheral or central vasculature. The vascular access device may be indwelling for short term (days), moderate term (weeks), or long term (months to years). The vascular access device may be used for continuous infusion therapy or for intermittent therapy.
A common vascular access device is a plastic catheter that is inserted into a patient's vein. The catheter length may vary from a few centimeters for peripheral access to many centimeters for central access by devices such as central vascular catheters (CVC) and peripherally inserted central catheters (PICC). The catheter may be inserted transcutaneously or may be surgically implanted beneath the patient's skin. The catheter, or any other vascular access device attached thereto, may have a single lumen or multiple lumens for infusion of many fluids simultaneously.
The vascular access device commonly includes a Luer adapter to which other medical devices may be attached. For example, an administration set may be attached to a vascular access device at one end and an intravenous (IV) bag at the other. The administration set is then a fluid conduit for the continuous infusion of fluids and pharmaceuticals. Commonly, an IV access device is attached to another vascular access device that acts to close the vascular access device, thus allowing for the intermittent infusion or injection of fluids and pharmaceuticals. An IV access device may include a housing and septum for closing the system, the latter of which may be opened with a blunt cannula or male Luer of a medical device.
Accessing the vascular access device could lead to certain complications due to several factors, such as contamination. Complications associated with infusion therapy may cause significant morbidity and even mortality. One significant complication is catheter related blood stream infection (CRBSI). An estimated 250,000-400,000 cases of central venous catheter (CVC) associated blood stream infections (BSIs) occur annually in US hospitals. Attributable mortality is an estimated 12%-25% for each infection and costs the health care system $25,000-$56,000 per episode.
A vascular access device may serve as a nidus of infection, resulting in a disseminated BSI. This may be caused by failure to regularly flush the device, a non-sterile insertion technique, or by pathogens that enter the fluid flow path through either end of the path subsequent to catheter insertion. When a vascular access device is contaminated, pathogens adhere to the vascular access device, colonize, and form a biofilm. The biofilm is resistant to most biocidal agents and provides a replenishing source of pathogens to enter a patient's bloodstream and cause a BSI. Thus, devices with antimicrobial properties are needed.
One approach to preventing biofilm formation and patient infection is to provide an antimicrobial coating on various medical devices and components. Over the last 35 years, it has been common practice to use a thermoplastic polyurethane solution as the carrier for antimicrobial coatings. The solvent is usually tetrahydrofuran (THF), dimethylformamide (DMF), or a blend of both. Since THF can be oxidized very quickly and tends to be very explosive, an expensive explosion-proof coating facility is necessary. These harsh solvents also attack many of the polymeric materials commonly used, including polyurethane, silicone, polyisoprene, butyl rubber polycarbonate, rigid polyurethane, rigid polyvinyl chloride, acrylics, and styrene-butadiene rubber (SBR). Therefore, medical devices made with these materials can become distorted over time and/or form microcracks on their surfaces. Another issue with this type of coating is that it takes almost 24 hours for the solvent to be completely heat evaporated. Accordingly, conventional technology has persistent problems with processing, performance, and cost.
Another limitation is the availability of suitable antimicrobial agents for use in such coatings. One of the most commonly used antimicrobial agents used in coating medical devices is silver, as described in U.S. Pat. No. 4,933,178. Silver salts and elemental silver are well known antimicrobial agents in both the medical surgical industry and general consumer products industries. They are usually incorporated into the polymeric bulk material or coated onto the surface of the medical devices by plasma, heat evaporation, electroplating, or conventional solvent coating technologies. These technologies are tedious, expensive, and not environmentally friendly.
In addition, the performance of silver coated medical devices is mediocre at best. For example, it can take up to eight (8) hours before the silver ion, ionized from silver salts or elemental silver, to be efficacious as an antimicrobial agent. As a result, substantial microbial activity can occur prior to the silver coating even becoming effective. Furthermore, many antimicrobial coatings with a silver compound or elemental silver are opaque, thus preventing the visualization of the fluid path in a vascular access device. Such visualization could be important to practitioners as an indicator of the progress of IV therapy. Added processing steps and cost are needed to improve the transparency of silver based antimicrobial coatings, as described in U.S. Pat. No. 8,178,120.
In U.S. Pat. Appl. No. 20100135949, Ou Yang disclosed a UV curable antimicrobial coating that was much cheaper to process and possessed superior antimicrobial efficacy in comparison to silver based antimicrobial coatings technology. However, a rheology modifier was required of this composition to prevent phase separation of the insoluble antimicrobial agent from the rest of the coating composition. The use of the rheology modifier increases the coating viscosity substantially, thus prohibiting the use of spraying as a coating application method. Accordingly, a solvent must be added to the coating composition to achieve a workable, sprayable viscosity, as described in U.S. Pat. Appl. No. 20100137472. The use of a solvent may be undesirable, as indicated above. Further, the addition of a solvent to lower the viscosity of the coating composition will result in increased phase separation of the antimicrobial agent within the coating composition.
Accordingly, there is a need in the art for improved compositions that impart antimicrobial capability to medical devices of various types, particularly devices related to infusion therapy. Specifically, there is a need for an effective antimicrobial coating that can be easily applied to medical devices constructed of polymeric materials and metals. There is also a need for improved methods of applying such antimicrobial coatings to medical devices. Further, there is a need for an effective antimicrobial coating comprising insoluble antimicrobial agents that are evenly disbursed within the matrix of the coating composition without observable phase separation.